AntibactERial Activity of Four Cephalosporins in an ExpERimental Infection in Relation to In Vitro Effect and Pharmacokinetics

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Abstract
The in vitro activity offour cephalosporins was compared with theireffects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parametERs ofthe plasmaconcentrations in vivo and those ofthe Hill equation thecorresponding time course of ER was calculated and by integration with respect to time (∫0tERdt), an estimate was obtained of the effect on bactERia . For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.